Page 33 - Ethical Guidelines for Conducting Research Studies Involving Human Subjects

type of trial, an indeterminate result was found due to
difference in clinical thought against statistical thinking.
Then this concept arose. In superiority trials one of the arms
can be placebo or active control but in equivalence trials use
of placebo arm will be unethical as the drug’s efficacy will
have to be tested against a proven therapy.

To improve reporting of RCT with primary focus on 2
parallel groups that assess the possible superiority of one
treatment compared with another, CONSORT (Consolidated
Standards of Reporting Trials) Statement, including a
checklist and a flow diagram, was developed in late 90s. As
in medical literature, the reporting method of non-inferiority
or ACET trials has been modified. CONSORT guidelines are
now being extended to other trial designs too.

Monitoring and reporting adverse reactions or events:

In drug trial any adverse event or adverse drug reaction (AE/ ADR),
expected and unexpected, should be specified in the concerned SOP. These
reactions can be mild, moderate or severe and causality relationship
should be examined. When an AE or unexpected ADR happens, it needs
expedited review by the ethics committee. Unexpected AE/ ADRs and all
SAE (serious adverse event) should be reported to the sponsor by the
investigator within 24 hours and to the ethics committee that accorded
approval to the study protocol within seven days. In the event of death the
NREC should also be informed within 24 hours. During a clinical trial if
any unexpected SAE as defined in the GCP (Good Clinical Practice)
Guidelines occurs should be communicated promptly within 14 calendar
days by the Sponsor to the Licensing Authority and to the Investigator(s)
of other trial sites participating in the study, so that the regulatory
authority can immediately stop the clinical trials of unapproved drugs or
withdraw from market approved drugs based on report of Phase IV
studies. All other serious unexpected reactions (ADRs) that are not fatal or
life threatening must be filed as soon as possible but not later than 14
calendar days. At the end of the trial, all adverse events whether related to
trial or not are to be listed, evaluated and discussed in detail in the final
report.

The medical management of the adverse event is the responsibility of the
investigator, and the protocol for adverse event management with
allocation of responsibilities must be pre-defined in the protocol and
submitted to the Ethics Committee. There must be a financial plan
(including, if available, insurance) to manage adverse events and
compensation for trial related injury. The Ethics Committee reviewing the
protocol, must review these aspects also before giving approval.

BMRC ETHICAL GUIDELINE ON HUMAN SUBJECTS Page 29